The reactions between lipid hydroperoxides and some important hemeproteins, in both the absence and presence of other biological compounds, will be characterized in detail. The reaction kinetics will be determined over a wide range of experimental conditions by spectrophotometric techniques, which measure directly chemical modifications of the heme prosthetic group of the protein. Electron paramagnetic resonance (EPR) spin trapping techniques, which will be applied to biological systems for the first time in this study, are expected to provide definitive evidence on the involvement and identity of free radical intermediates in these reactions. Heme degradation products will be identified by thin layer chromatography, used in conjunction with radioactive isotope assays and mass spectrometry. In similar studies, the reactions of hematin with lipid hydroperoxides, in both aqueous and non-aqueous systems, will be investigated as models for the corresponding hemeprotein reactions. The goals of these studies are to elucidate the molecular mechanism of hemeprotein-lipid hydroperoxide reactions and also the dependence of hemeprotein reactivity on the structure and biological function of the protein. These results will define more clearly the physiological role of lipid hydroperoxides in two important aspects of hemeprotein biochemistry: (1) Heme degradation in vivo to bile pigments; and (2) The enzymic functions of membrane-bound hemeproteins, such as microsomal cytochrome P-450, which can both promote the peroxidation of membrane lipids and react further with the lipid hydroperoxides so formed.